Lysophosphatidic acid, LPA, is a phospholipid signalling molecule that has a wide variety of effects on many different cell types (Moolenaar, 1995, Curr. Opin. Cell Biol. 7:203-210), including neuronal cells. Possible functions of LPA in cortical neurogenesis, based on known bioactivities of LPA and biological events occurring within the ventricular zone of the cerebral cortex, include regulation of cytoskeletal events such as interkinetic nuclear movement, cell rounding, and cleavage plane orientation, mitogenesis, gap junction regulation and influence on the binding and assembly of fibronectin which is expressed in the embryonic cortex. Additionally, regulation of apoptosis, recently shown to occur in the vz may also be influenced by LPA signalling. Further, recent evidence implicates LPA in the proliferation of certain cancer cells (Xu et al. 1995, J. Cell Physiol. 163:441-450).
Although LPA is believed to act through a G-protein coupled receptor (GPCR), a cDNA clone of this receptor has not been identified, in part reflecting the chemical characteristics of LPA that result in unacceptably high levels of non-specific binding, making techniques such as expression cloning impractical for discovery of this receptor.